Author/Authors :
Mark A. Collins، نويسنده , , Valerie Hudak، نويسنده , , Reinhold Bender، نويسنده , , Andrew Fensome، نويسنده , , Puwen Zhang، نويسنده , , Lori Miller، نويسنده , , Richard C Winneker، نويسنده , , Zhiming Zhang، نويسنده , , Yuan Zhu، نويسنده , , Jeffrey Cohen، نويسنده , , Rayomond J Unwalla، نويسنده , , Jay Wrobel، نويسنده ,
Abstract :
A series of 1,4-dihydro-2H-[d][3,1]-benzoxazin-2-one and 1,3-dihydro-[3H]-indol-2-one containing 6- or 5-, respectively, appended substituted pyrrole moieties were synthesized and evaluated for their ability to modulate the activity of the progesterone receptor (PR). Key structural changes to the pyrrole moieties of these molecules were shown to have a predictive influence as to whether the compounds behaved as PR agonists or antagonists. Compounds with the 5′-cyano-2′-pyrrole moiety (e.g., 32, 33, and 38) were shown to be potent PR agonists (EC50ʹs of 1.1, 1.8, and 2.8 nM, respectively). Compounds with the 5′-nitro-2′-pyrrole moiety (e.g., 34 and 36) were shown to be PR antagonists (IC50ʹs of 180 and 36 nM, respectively).
